The present disclosure relates to crystalline forms of 5-(2,4-diamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-benzenesulfonamide (“Compound A”) or a salt thereof.
The respiratory tract, or airways, participates in the vital process of gas exchange in order to support the demand for oxygen intake and carbon dioxide elimination. Vagal autonomic nerves control smooth muscles of the tracheobronchial tree, and thus caliber of airways, as well as liberation and movement of secretions (mucus and fluid). Control is coordinated within brainstem nuclei which regulate voluntary and autonomic outflow, relying on a rich input of vagal sensory signals from the airway tissues that in turn convey conscious sensation and trigger autonomic reflexes. Vagal sensory fibers arise mostly from cell bodies within jugular and nodose ganglia, and their activity is regulated by a range of chemical substances such as ATP, which sensitizes vagal afferents and serves as a convergent mechanosensory airways signal.
ATP activates purinoceptors (e.g., P2X3 and P2X2/3), which mediate many physiological and pathological roles. ATP stimulates and sensitizes sensory nerve endings resulting in intense sensations such as pain, discomfort, urgency, itch and urge and a pronounced increase in sensory nerve discharge, largely via P2X3 receptor activation on afferent nerve fibers innervating rodent and human tissues and organs, especially the hollow viscera.
Compound A is described in International Publication WO2005/095359 (published on Oct. 13, 2005) and U.S. Pat. No. 7,858,632 (published Sep. 22, 2005), which are hereby incorporated by reference in their entireties. Compound A is a P2X3 and/or P2X2/3 inhibitor(s) and is potentially useful for the treatment of cough, chronic cough and urge to cough in respiratory conditions and disorders, among other conditions.